DISCUSSION
Respiratory viruses are among the leading causes of pediatric morbidity
and mortality worldwide. Unlike other viral respiratory diseases,
COVID-19 has had a relatively limited impact on children as compared to
adults.9 However, as lockdowns are eased and schools
reopened, the increased contact between unvaccinated children might
change the scenario and increase the circulation of both SARS-CoV2 and
other respiratory viruses, including influenza.10
In this cohort comparing the clinical characteristics and outcomes of
SARS-CoV2 infection with epidemic influenza in hospitalized pediatric
patients in a single referral hospital, we found a higher proportion of
asymptomatic infection in children with SARS-CoV2 than in those with
influenza. Almost half of infants with SARS-CoV2 infection had no
symptoms of COVID-19. However, the greater proportion of asymptomatic
infection may be explained by the different sampling approach, with PCR
testing performed on all admissions beginning in June.
Fever and cough were the most common manifestations among both groups,
but rhinorrhea was rare in patients with COVID-19 while it was common in
children with influenza. The absence of nasal symptoms might be
suggestive of COVID-19 in pediatric patients with fever and cough.
However, most signs and symptoms were similar between the two groups,
making clinical distinction unreliable.
In comparison, in a retrospective cohort of 315 pediatric patients with
COVID-19 (median age 8.3 years) and 1402 with influenza (median age 3.9
years) in the Unites States, Song et al.11 describe a
higher frequency of fever, gastrointestinal symptoms, headache, myalgia
and chest pain among hospitalized children with COVID-19. However,
patients with COVID-19 were older than those with influenza (median age
8.3 years, versus 3.9 years) which might have biased the reporting of
symptoms.
Another retrospective single-center cohort study found a lower Charlson
index in the COVID-19 group, as well as a greater frequency of anosmia,
dysgeusia, diarrhea and frontal headache, and lower prevalence of
dyspnea, conjunctivitis and vomiting. No children were included in this
cohort.12
Regarding outcome, hospitalized patients with symptomatic influenza and
COVID-19 had a similar risk of invasive mechanical ventilation and
death, and one in ten infants had a fatal outcome. This underscores that
even though COVID-19 is usually mild in children, it can cause severe
disease and death in children with chronic diseases, as has been
recognized for influenza for a long time4. Mortality
was lowest among children 1 to 9 years old with either influenza or
SARS-CoV2 infection, but differences between age groups were not
statistically significant. This is consistent with reports from the
United States, where the greatest proportion of COVID-19 pediatric
deaths occurred in infants and adolescents13 and
deaths from influenza are more frequent among those younger than 6
months.14
The aforementioned study by Song et al.11 reported a
similar rate of hospitalization, intensive care unit admission and use
of mechanical ventilation. Two deaths were reported among patients with
influenza while no patients with COVID-19 died.
In France, Piroth et al.15 describe a higher
in-hospital mortality for patients with COVID-19 in comparison with
those with influenza, based in a nationwide retrospective cohort of
hospitalized patients. The proportion of pediatric patients was smaller
for COVID-19 than for influenza, but in-hospital mortality was ten-times
greater for COVID-19 in those 11-17 years old, and a larger proportion
of patients younger than 5 years needed intensive care support for
COVID-19 than for influenza.
A systematic review and meta-analysis of studies describing individuals
with either influenza or COVID-19 reported a lower frequency of nasal
symptoms, pharyngodynia and dyspnea, and a greater prevalence of
radiographic abnormalities among patients with COVID-19. Case fatality
rate of hospitalized patients was 6.5%, 6% and 3% respectively for
individuals with COVID-19, influenza A and influenza B. However,
pediatric patients represented a small fraction of the cases and
findings were limited by the heterogeneity of the
studies.16
Zhang et al.17 describe two cohorts of patients
hospitalized with influenza or COVID-19 in two separate locations. One
in every five patients with COVID-19 was admitted to ICU and 13% died,
while no severe or fatal cases were recorded in the influenza cohort. No
data for pediatric patients was reported in this study.
Our study has several limitations worth noting. The single-center nature
of the cohort, as well as the frequency of comorbidities among
participants, may limit the generalizability of findings. Data on
patients with influenza was collected retrospectively from clinical
records while the COVID-19 cohort was followed-up prospectively. The
different time periods between the two cohorts may account from
differences in diagnostic and therapeutic approaches. As mentioned
above, all patients admitted to hospital were screened for SARS-CoV2
infection from June 2020, which explains the greater proportions of
asymptomatic infections. However, asymptomatic patients were excluded
from the outcome analysis to account for this limitation. Non-invasive
mechanical ventilation was discouraged for patients with suspected or
confirmed COVID-19 to reduce aerosol generation, which might have
increased the proportion of patients receiving invasive mechanical
ventilation.
In conclusion, influenza and COVID-19 have a similar picture in
pediatric patients, which makes diagnostic testing necessary for
adequate diagnosis and management and will add to the challenge of
co-circulation as SARS-CoV2 becomes endemic. Even though most cases of
COVID-19 in children are asymptomatic or mild, the risk of death among
hospitalized children with comorbidities is substantial, especially
among infants, and is similar to that of patients with influenza. Thus,
children should not be left out of preventive and therapeutic
development in the COVID-19 pandemic, including vaccine development
programs.18